Online-Ressource | |
Verfasst von: | Trova, Sandro [VerfasserIn] |
Lin, Fei [VerfasserIn] | |
Lomada, Santosh K. [VerfasserIn] | |
Fenton, Matthew [VerfasserIn] | |
Chauhan, Bhavini [VerfasserIn] | |
Adams, Alexandra [VerfasserIn] | |
Puri, Avani [VerfasserIn] | |
Maio, Alessandro Di [VerfasserIn] | |
Wieland, Thomas [VerfasserIn] | |
Sewell, Daniel [VerfasserIn] | |
Dick, Kirstin [VerfasserIn] | |
Wiseman, Daniel [VerfasserIn] | |
Wilks, Deepti P. [VerfasserIn] | |
Goodall, Margaret [VerfasserIn] | |
Drayson, Mark T. [VerfasserIn] | |
Khanim, Farhat L. [VerfasserIn] | |
Bunce, Christopher M. [VerfasserIn] | |
Titel: | Pathogen and human NDPK-proteins promote AML cell survival via monocyte NLRP3-inflammasome activation |
Verf.angabe: | Sandro Trova, Fei Lin, Santosh Lomada, Matthew Fenton, Bhavini Chauhan, Alexandra Adams, Avani Puri, Alessandro Di Maio, Thomas Wieland, Daniel Sewell, Kirstin Dick, Daniel Wiseman, Deepti P. Wilks, Margaret Goodall, Mark T. Drayson, Farhat L. Khanim, Christopher M. Bunce |
Jahr: | 2023 |
Umfang: | 23 S. |
Fussnoten: | Veröffentlicht: 7. Juli 2023 ; Gesehen am 28.08.2023 |
Titel Quelle: | Enthalten in: PLOS ONE |
Ort Quelle: | San Francisco, California, US : PLOS, 2006 |
Jahr Quelle: | 2023 |
Band/Heft Quelle: | 18(2023), 7, Artikel-ID e0288162, Seite 1-23 |
ISSN Quelle: | 1932-6203 |
Abstract: | A history of infection has been linked with increased risk of acute myeloid leukaemia (AML) and related myelodysplastic syndromes (MDS). Furthermore, AML and MDS patients suffer frequent infections because of disease-related impaired immunity. However, the role of infections in the development and progression of AML and MDS remains poorly understood. We and others previously demonstrated that the human nucleoside diphosphate kinase (NDPK) NM23-H1 protein promotes AML blast cell survival by inducing secretion of IL-1β from accessory cells. NDPKs are an evolutionary highly conserved protein family and pathogenic bacteria secrete NDPKs that regulate virulence and host-pathogen interactions. Here, we demonstrate the presence of IgM antibodies against a broad range of pathogen NDPKs and more selective IgG antibody activity against pathogen NDPKs in the blood of AML patients and normal donors, demonstrating that in vivo exposure to NDPKs likely occurs. We also show that pathogen derived NDPK-proteins faithfully mimic the catalytically independent pro-survival activity of NM23-H1 against primary AML cells. Flow cytometry identified that pathogen and human NDPKs selectively bind to monocytes in peripheral blood. We therefore used vitamin D3 differentiated monocytes from wild type and genetically modified THP1 cells as a model to demonstrate that NDPK-mediated IL-1β secretion by monocytes is NLRP3-inflammasome and caspase 1 dependent, but independent of TLR4 signaling. Monocyte stimulation by NDPKs also resulted in activation of NF-κB and IRF pathways but did not include the formation of pyroptosomes or result in pyroptotic cell death which are pivotal features of canonical NLRP3 inflammasome activation. In the context of the growing importance of the NLRP3 inflammasome and IL-1β in AML and MDS, our findings now implicate pathogen NDPKs in the pathogenesis of these diseases. |
DOI: | doi:10.1371/journal.pone.0288162 |
URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt. kostenfrei: Volltext: https://doi.org/10.1371/journal.pone.0288162 |
kostenfrei: Volltext: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0288162 | |
DOI: https://doi.org/10.1371/journal.pone.0288162 | |
Datenträger: | Online-Ressource |
Sprache: | eng |
Sach-SW: | Cell differentiation |
Flow cytometry | |
Inflammasomes | |
Monocytes | |
Secretion | |
Transcription factors | |
Vitamins | |
White blood cells | |
K10plus-PPN: | 1858024978 |
Verknüpfungen: | → Zeitschrift |